Effect of Mild Traumatic Brain Injury on Behavioral Reactions and Neocortical Morphology in Rats.

The original weight-drop model was employed to examine the effect of mild traumatic brain injury (TBI) on behavioral phenotype and neocortical morphology in rats. The neurological examination of rats with moderate TBI revealed the focal symptoms corresponding to pronounced neurological disorders, whereas in rats after mild TBI, there were only minor coordination disorders. On day 7 after injury, the rats with mild TBI demonstrated enhanced anxiety assessed by conditioned passive avoidance response. The morphometric analysis of the brain tissues revealed narrowing of the capillaries and increased score of hyperchromic neocortical neurons, which attested to cerebral hypoxia. The manifestations of mild TBI in original rat model demonstrated a close similarity to the symptoms of TBI in humans.

Effect of Hypotensive Drugs on Dynamics of Nitroxide-Producing Renal Function in Rats with Nephrogenic Hypertension.

An original model of nephrogenic hypertension in rats was used for histochemical mapping of NADPH diaphorase (NO synthase) in various renal segments to examine the effect of hypotensive drugs furosemide, bendazol, and clonidine on the time course of nitroxide production in the kidneys. In various nephron segments, these drugs modulated NO synthesis in different ways. Clonidine induced a stable up-regulation of NO synthesis, which can maintain active vasodilation and gradually diminish the rennin production. Bendazol also enhanced NO synthase activity in renal glomeruli and collecting tubules, but this effect was less pronounced and short lasting. During the first week after injection of bendazol, insignificant elevation of NO synthase activity was observed in the proximal nephron segments. Furosemide exerted the least effect on NO production in kidneys.

Specific features of analgesic effect of docosahexaenoic acid in rats with neuropathic pain syndrome.

Experiments on white rats showed that sciatic nerve ligation induced the development of neuropathic pain syndrome: thermal pain threshold decreased, significant reduction in weight bearing of the injured limb, and degenerative changes in the foot tissues. Administration of docosahexaenoic acid reduces activity and duration neuropathic pain syndrome, promoted reversion of weight bearing asymmetry, and prevented the development of degenerative changes in the foot tissues.

Histo- and immunocytochemical detection of inducible NOS and TNF-alpha in the locus coeruleus of human opiate addicts.

In order to determine the role of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of opiate addiction in humans, the expression of both was analyzed in the locus coeruleus (LC) of patients who died from heroin overdose. In control subjects, NADPH-diaphorase (NADPHd) histochemistry was mainly observed in non-noradrenerdic neurons, some glial and endothelial cells. However, in the brain of opiate addicts, NADPHd and iNOS expression was detected in noradrenergic LC cells, correlating with an increase in iNOS and TNF-alpha expression in glial cells as revealed by immunohistochemical and Western blot analyses. These findings indicate that sustained overproduction of cytokine and NO via iNOS expression may be responsible, at least in part, for some neurochemical changes in the locus coeruleus caused by chronic opiate usage in humans.

Effects of NO-modulating agents on the development of acute painful reaction in rats.

Painful reaction of rats to intraperitoneal injections of L-arginine, Nw-nitro-L-arginine, and agmatine was studied on the model of formalin-induced inflammation. All drugs exhibited a dubious effect on the patterns of nociceptive behavior depending on the phase of painful reaction. The dynamics of nitrate/nitrite content in animal blood and serum indicated the presence of NO-dependent and NO-independent components in the mechanisms of pharmacological effects of these drugs.

Neurochemical diversity of neurogliaform cells in the human primary motor cortex.

Neurogliaform cells of area 4 of the human motor cortex were found to express choline acetyl transferase (ChAT), gamma-aminobutyric acid, and calbindin. GABA- and calbindin-positive NGCs were mainly localized in layers II and VI and were relatively rare in layer I of the cortex. ChAT-positive NGCs were observed in the upper and middle thirds of layer II, occurring occasionally in layer I and the upper portion of layer III. Their numbers were low compared to those of GABA- and calbindin-positive NGCs in layers II/III. The dendrites of ChAT-positive NGCs were short and few in number. Axonal arborizations of neighboring ChAT-positive cells interpenetrated considerably so that each ChAT-positive cell body was normally surrounded by axonal trees of the parent and a few other ChAT-positive NGCs. NGC axon collaterals surrounded small neuropil areas containing perikarya presumptive pyramidal neurons. The findings are discussed in the context of information processing in cortical modules and interaction of excitatory and inhibitory interneurons.

Induction of NO synthase and glial acidic fibrillary protein in astrocytes in the temporal cortex of the rat with audiogenic epileptiform reactions.

The localizations of NADPH-diaphorase (NADPH-d), inducible NO synthase (iNOS), and glial acid fibrillary protein (GFAP) in astrocytes of the temporal cortex were studied in Krushinskii-Molodkina rats, which are genetically predisposed to audiogenic convulsive seizures. Convulsive reactions were induced in rats by three exposures to acoustic stimuli. Controls consisted of Wistar rats and Krushinskii-Molodkina rats not subjected to acoustic stimulation, these not developing convulsive reactions. The neocortex of animals with audiogenic convulsions consistently showed foci of brain tissue damage. Foci, of diameter 300-400 microm, were located in layers III-V and were groupings of NADPH-d-positive astrocytes; these were seen in both hemispheres. Astrocytes in foci of damage expressed iNOS and had elevated GFAP levels. The numbers of GFAP-immunopositive cells were increased by 25-37% in damage foci as compared with levels in controls and undamaged areas of the cortex. The induction of NO synthase and GFAP in astrocytes seen here indicates the involvement of glia in compensatory NO-dependent mechanisms formed in damage foci in response to audiogenic convulsive seizures.

NO-ergic neurons of the cervical nucleus of the rat brain in normal conditions and after administration of opiates.

Histochemical reactions for NADPH-diaphorase (NADPH-d) were used to study the dynamics of NO synthesis activity in the cervical nuclei of the rat brain after i.v. administration of morphine hydrochloride. In normal conditions, NADPH-d activity was found in neurons in all the cervical nuclei. Acute and chronic administration of morphine at different doses (0.5 and 5 mg/kg) suppressed the NO-ergic activity of most cervical neurons. Decreases in the level of NADPH-d activity were different in different nuclei. NO-ergic changes were due to activation of opiate receptors, as they were dependent on the dose of morphine used, and treatment with the opiate antagonist naloxone restored the NO-ergic function of cervical neurons. Formation of tolerance to the analgesic effect of opiates was accompanied by significant but short-lived increases in NO synthesis activity. It is suggested that changes in the NO-ergic functions of cervical neurons may affect the balance of serotonin in the brain during opiate treatment.

Ethanol-oxidizing and NO-synthesizing enzymes in monoaminergic nuclei of human brain.

Serotonin-, dopamine-, and noradrenergic nuclei in human brainstem were examined histochemically for alcohol dehydrogenase, aldehyde dehydrogenase, and NADPH diaphorase. The findings indicate that monoaminergic centers are characterized by different repertoire of NO-ergic and ethanol-oxidizing enzymes, whose distribution correlates with the transmitter specialization of neurons.

NO-ergic neurons of rat nucleus gracilis during acute pain.

Histochemical staining for NADPH diaphorase showed that the number of NO-ergic neurons in the nucleus gracilis of rat brain increased within the first few hours of pain stimulation. Initially, the changes were noted on the side of lesion, but then involve both halves of the nucleus. It was assumed that nucleus gracilis participates in processing of acute pain information.

Dynamics of NADPH diaphorase activity in raphe neurons during chronic treatment with opiates.

Systemic administration of diacetylmorphine considerably reduced the number of NADPH diaphorase-positive (NO-synthesizing) neurons in rat brain raphe nuclei. This effect was blocked by naloxone. In animals with the withdrawal syndrome NO-ergic activity in raphe neurons increased and surpassed the normal.